GENISTEIN INHIBITS GROWTH OF B16 MELANOMA-CELLS IN-VIVO AND IN-VITRO AND PROMOTES DIFFERENTIATION IN-VITRO

Consumption of soy products has been linked to a reduced mortality and morbidity from a number of cancers. Genistein, one of the principal s oy isoflavones, has been shown to inhibit the growth of a number of tu mour cell lines in vitro; however, a role of genistein in retarding tu mour growth in vivo is less well documented. In this study, in additio n to examining the effects of genistein on the growth of murine B16 me lanoma cells in vitro, we have examined the effects of feeding a genis tein-rich diet on s.c. growth of these tumour cells in mice. In vitro, the melanoma cells showed an increase in sensitivity to genistein wit h increasing time of exposure, culminating in a 50% growth inhibition (IC50) at 12.5 mu M after 7 days. Genistein at 25 mu M induced micronu cleus formation after 24 hr and at concentrations as low as 2.5 mu M i nduced morphological changes indicative of differentiation. Growth of solid tumours implanted into female C57BL/6J mice was inhibited by 50% when mice were fed genistein for 1 week before and for 1 week after i noculation with B16 melanoma cells. Plasma genistein concentrations at the time of tumour removal were 1.1 mu M, which is similar to levels reported in humans consuming diets high in soybeans or soybean product s, while control animals had no detectable genistein in plasma. Our re sults provide additional in vivo evidence suggesting that genistein re tards the growth of implanted tumours, adding further to studies sugge sting that this isoflavonoid is a biologically active component of soy foods. (C) 1997 Wiley-Liss, Inc.